Vasodilating or antidepressant phenalkanolaminoalkyl-substituted imidazolidinones

ABSTRACT

Racemic and optically active compounds of the formula 
     
         Q--C.sub.n H.sub.2n --NH--R 
    
     wherein 
     Q is ##STR1##  where R 1  is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, trifluoromethyl or amino, 
     R 2  is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atomsor trifluoromethyl, 
     R 1  and R 2 , together with each other, are methylenedioxy or ethylenedioxy, and 
     A is --O--, --CH 2  --CH 2  --, or --NR 3  -- where R 3  is hydrogen or alkyl of 1 to 4 carbon atoms, 
     n is an integer from 2 to 6, inclusive, and 
     R is hydrogen, benzyl or ##STR2##  where R 4  is hydrogen, methyl or ethyl, 
     R 5 , R 6  and R 7 , which may be identical to or different from each other, are each hydrogen, halogen, hydroxymethyl, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro, cyano, --CONHR 3 , --CONHOH, --COOR 3 , R 8  O--, methylsulfonylmethyl or, when one or two of R 5  through R 7  are other than halogen or trifluoromethyl, also--NR 3  R 9 , 
      where 
     R 3  has the meanings defined above, 
     R 8  is hydrogen, alkanoyl of 1 to 20 carbon atoms, alkyl of 1 to 4 carbon atoms, or aralkyl, and 
     R 9  is hydrogen, lower alkanoyl, methanesulfonyl, carbamoyl, dimethylsulfamoyl, or alkoxycarbonyl of 2 or 5 carbon atoms, and 
     R 5  and R 6 , together with each other, are --O--CH 2  --O, --O--CH 2  --CH 2  --O--, --CH═CH--CH═CH--, --O--CH 2  --CONH--, --CH 2  --CH 2  --CONH-- or --O--CO--NH--, 
      and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds as well as their salts are useful as vasodilators and CNS- stimulators.

CROSS REFERENCE TO RELATED APPLICATION

This application is a division of U.S. Pat. application Ser. No. 026,608, filed Apr. 3, 1979, which in turn is a continuation-in-part of U.S. patent application Ser. No. 773,394 filed Mar. 2, 1977, now U.S. Pat. No. 4,154,829, incorporated herein by reference.

This invention relates to novel aminoalkyl-substituted heterocycles and non-toxic salts thereof, as well as to various methods of preparing these compounds.

More particularly, the present invention relates to a novel class of aminoalkyl-substituted heterocycles represented by the formula

    Q--C.sub.n H.sub.2n --NH--R                                (I)

wherein

Q is ##STR3## where R₁ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, trifluoromethyl or amino,

R₂ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or trifluoromethyl,

R₁ and R₂, together with each other, are methylenedioxy or ethylenedioxy, and

A is --O--, --CH₂ --CH₂ --, or --NR₃ -- where R₃ is hydrogen or alkyl of 1 to 4 carbon atoms,

n is an integer from 2 to 6, inclusive, and R is hydrogen, benzyl or ##STR4## where R₄ is hydrogen, methyl or ethyl,

R₅, R₆ and R₇, which may be identical to or different from each other, are each hydrogen, halogen, hydroxymethyl, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro, cyano, --CONHR₃, --CONHOH, --COOR₃, R₈ O--, methylsulfonylmethyl or, when one or two of R₅ through R₇ are other than halogen or trifluoromethyl, also --NR₃ R₉,

where

R₃ has the meanings defined above,

R₈ is hydrogen, alkanoyl of 1 to 20 carbon atoms, alkyl of 1 to 4 carbon atoms or aralkyl, and

R₉ is hydrogen, lower alkanoyl, methanesulfonyl, carbamoyl, dimethylsulfamoyl, or alkoxycarbonyl of 2 to 5 carbon atoms, and

R₅ and R₆, together with each other, are --O--CH₂ --O, --O--CH₂ --CH₂ --O--, --CH═CH--CH═CH--, --O--CH₂ --CONH--, --CH₂ --CH₂ --CONH-- or --O--CO--NH--,

and non-toxic, pharmacologically acceptable acid addition salts thereof.

The alkylene chain --C_(n) H_(2n) -- in formula I may be straight or branched, and preferred embodiments thereof are --CH₂ --CH₂ --, --CH₂ --CH₂ --CH₂ --, --CH₂ C(CH₃)₂ -- and primarily --CH₂ CH₂ --C(CH₃)₂ --, where the tertiary carbon atom is bonded to the nitrogen atom or the --NH--R moiety.

A subgenus thereunder is constituted by compounds of the formula I, wherein

Q, A and R₃ have the meanings previously defined,

R₁ is hydrogen, methoxy or amino,

R₂ is hydrogen or methoxy,

n is an integer from 3 to 6, inclusive,

R is hydrogen or ##STR5## R₅ is hydrogen, --OR₈, --NHR₉, hydroxymethyl, cyano, --CONHR₃ or halogen.

R₆ is hydrogen, hydroxyl or halogen,

R₇ is hydrogen, chlorine, methyl or methoxy,

R₈ is hydrogen, benzyl, methyl or alkanoyl, and

R₉ is hydrogen, formyl, acetyl, methylsulfonyl, carbamoyl or dimethylsulfamoyl,

provided that, when R₆ and/or R₇ are halogen, R₅ is other than --NHR₉ ; and non-toxic, pharmacologically acceptable acid addition salts thereof.

A particularly preferred subgenus thereunder is constituted by compounds of the formula I, wherein

Q, A, R₃, R₄ and n have the meanings previously defined,

R₁ is hydrogen, methoxy or amino,

R₂ is hydrogen or methoxy,

R is hydrogen or ##STR6## R₅ is hydrogen or hydroxyl, R₆ is hydrogen, hydroxyl, hydroxymethyl, cyano, --CONHR₃, --OR₈ or chlorine,

R₅ and R₆, together with each other, are --CH═CH--CH═CH--, --OCH₂ --CONH--, --CH₂ --CH₂ --CONH-- or --O--CONH--,

R₇ is hydrogen, methyl, methoxy, hydroxyl or chlorine, and

R₈ is hydrogen, benzyl or lower alkanoyl,

and non-toxic, pharmacologically acceptable acid addition salts thereof.

The compounds embraced by formula I may be prepared by the following methods, all of which involve known organic synthesis principles.

Method A

For the preparation of a compound of the formula I wherein R is a grouping of the formula III, by reacting an amine of the formula

    Q--C.sub.n H.sub.2n --NH.sub.2                             (IV)

wherein Q and n have the same meanings as in formula I, with a compound of the formula ##STR7## wherein R₅, R₆ and R₇ have the same meanings as in formula I, and

R₁₀ is hydrogen or alkyl,

under reductive amination conditions. Suitable reducing agents are complex hydrides, preferably sodium borohydride, or hydrogen in the presence of a hydrogenation catalyst, preferably platinum, palladium or nickel.

Method B

For the preparation of a compound of the formula I wherein R is a grouping of the formula III, by reducing a compound of the formula ##STR8## wherein Q, n, R₄, R₅, R₆ and R₇ have the same meanings as in formula I, with a complex hydride, in particular sodium borohydride, or by catalytic hydrogenation with a conventional hydrogenation catalyst, for example, platinum, palladium or nickel.

Method C

For the preparation of a compound of the formula I, wherein R is a grouping of the formula III, by reacting an epoxide of the formula ##STR9## wherein R₄, R₅, R₆ and R₇ have the same meanings as in formula I, with an amine of the formula IV; or by reacting a halohydrin of the formula ##STR10## wherein R₄, R₅, R₆ and R₇ have the same meanings as in formula I, and

Hal is halogen,

with an amine of the formula IV in the presence of an acid binding agent, such as potassium carbonate, sodium carbonate or an excess of the amine IV. The halohydrin of the formula VIII converts into the corresponding epoxide VII under the reaction conditions.

Method D

For the preparation of a compound of the formula I wherein --C_(n) H_(2n) -- is ##STR11## where n has the same meanings as in formula I, and

R₁₁ is hydrogen or methyl,

by reductive amination of a compound of the formula ##STR12## wherein Q and n have the same meanings as in formula I, and

R₁₁ has the meanings defined above,

with an amine of the formula

    H.sub.2 N--R                                               (X)

wherein R has the same meanings as in formula I. Suitable reducing agents are complex hydrides, such as sodium borohydride, or hydrogen in the presence of a catalyst, such as platinum, palladium or nickel; or by reducing a compound of the formula ##STR13## wherein Q, n, R₄ and R have the meanings previously defined.

Method E

For the preparation of a compound of the formula I wherein R is a grouping of the formula III, by removing the --CH₂ -aryl protective group from a compound of the formula ##STR14## wherein Q, n, R₄, R₅, R₆ and R₇ have the same meanings as in formula I, by catalytic hydrogenation with a catalyst such as platinum, palladium or nickel.

Method F

For the preparation of a compound of the formula I in which at least one of substituents R₅, R₆ and R₇ is hydroxyl, by removing the arylmethyl protective group or groups from a corresponding compound wherein the respective hydroxyl substituent or substituents are arylmethylated. The removal of the arylmethyl group or groups is effected by catalytic hydrogenation with a catalyst such as platinum, palladium or nickel, or by ether cleavage with a hydrohalic acid or boron tribromide.

Method G

For the preparation of a compound of the formula I wherein R₅ is --NH-acyl or --NH--CO--NH₂, by reacting a compound of the formula ##STR15## wherein Q, n, R₄, R₆ and R₇ have the same meanings as in formula I, and

X is an anion,

with a carboxylic acid anhydride for introduction of the aryl radical, or with a cyanate and an acid for introduction of the carbamoyl radical. At least one mol of an acid, which protects the secondary amino group by salt formation, is additionally required.

Method H

For the preparation of a compound of the formula I wherein R₅ is --CONHR₃, --CONHNH₂ or --CONHOH, by reacting an ester of the formula ##STR16## wherein Q, n, R₄, R₆ and R₇ have the same meanings as in formula I, and

R" is alkyl or substituted alkyl,

with a compound of the formula

    NH.sub.2 --R.sub.12                                        (XV)

wherein R₁₂ is hydrogen, lower alkyl, hydroxyl or amino.

Method I

For the preparation of a compound of the formula I wherein R is hydrogen or benzyl, by removing the protective group or groups from a compound of the formula. ##STR17## wherein Q and n have the same meanings as in formula I,

R₁₃ is arylmethyl, acyl or --COOR₁₅,

R₁₄ is hydrogen or benzyl, and

R₁₃ and R₁₄, together with each other, are a dicarboxylic acid radical, such as succinyl or phthalyl, or --CHR₁₅ --,

where R₁₅ is alkyl, arylmethyl or aryl.

When R₁₃ is acyl or --COOR₁₅, or R₁₃ and R₁₄ together are a dicarboxylic acid radical or --CHR₁₅ --, the protective groups are removed by hydrolysis. When R₁₃ and R₁₄ together are a dicarboxylic acid radical, such as phthalyl, the removal may be effected by ring cleavage with hydrazine, followed by hydrolysis. When R₁₃ and/or R₁₄ are arylmethyl, the removal must be effected by hydrogenation in the presence of a catalyst, such as platinum, palladium or nickel. It is also possible to remove the protective group by catalytic hydrogenation when R₁₅ in --COOR₁₅ is arylmethyl.

Method J

For the preparation of a compound of the formula I wherein R is hydrogen, by reducing the nitro group in a compound of the formula

    Q--C.sub.n H.sub.2n --NO.sub.2                             (XVII)

wherein Q and n have the same meanings as in formula I, preferably by catalytic hydrogenation with conventional catalysts, such as nickel.

The starting compounds for methods A through J are either known compounds or may be prepared by known methods.

In those instances where the end products of methods A through J are racemates, these may be separated into the optical antipode components by conventional methods.

The compounds embraced by formula I are organic bases and therefore form acid addition salts with inorganic or organic acids. Examples of non-toxic, pharmacologically acceptable acid addition salts are those formed with hydrochloric acid, hydrobromic acid, sulfuric acid, maleic acid, succinic acid, formic acid, p-amino-benzoic acid, methanesulfonic acid, 8-chlorotheophylline or the like.

The following examples illustrate the present invention and will enable others skilled in the art to understand it more completely. It should be understood, however, that the invention is not limited solely to the particular examples given below.

EXAMPLE I

A mixture consisting of 5.36 gm of 3,4-dichlorophenyl-glyoxal hydrate, 4.5 gm of 1-(3-amino-n-propyl)-1,2,3,4-tetrahydro-quinolone-(2) and 200 ml of ethanol was heated at 50° C. for 1 hour. Then, while cooling, it was admixed with 5 gm of sodium borohydride at 0° to 5° C., the mixture was stirred for 2 hours at room temperature and then acidified with hydrochloric acid, the ethanol was distilled off, and the residue was made alkaline with ammonia. 5.5 gm of the free base, m.p. 95° C., of the formula ##STR18## were obtained. Its hydrochloride, m.p. 185° C., was obtained by admixing the free base with the calculated amount of ethereal hydrochloric acid.

EXAMPLE 2

A mixture consisting of 11 gm of 1-(3,4-dibenzyloxyphenyl)-1-oxo-2-hydroxy-2-ethoxyethane (m.p. 114° C.), 5.6 gm of 1-(3,3-dimethyl-3-amino-n-propyl)-benzimidazolinone-(2) and 225 ml of ethanol was heated for 3 hours and subsequently admixed at 0° to 5° C. with 8 gm of sodium borohydride. The resulting solution was allowed to stand at room temperature for 12 hours, and then acidified with hydrochloric acid and worked up as described in the proceeding example. 12.7 gm of free base, m.p. 130° C., of the formula ##STR19## were obtained. Its maleate, m.p. 197° C., was obtained by adding a solution of maleic acid in acetonitrile to the base.

Using procedures and starting compounds analogous to those described in Examples 1 and 2, the compounds shown in the following table were also prepared. The indicated yields are in % of theory.

                                      TABLE I                                      __________________________________________________________________________     Ex.                                      Yield %                                                                             M.P. of     m.p. of              No.                                                                               Formula                               of theory                                                                           Base °C.                                                                     Salt   Salt                 __________________________________________________________________________                                                               °C.               ##STR20##                            82   115                              4                                                                                  ##STR21##                            66        maleate                                                                               134                  5                                                                                  ##STR22##                            81        maleate                                                                               217                  6                                                                                  ##STR23##                            78   151                              7                                                                                  ##STR24##                            79        succinate                                                                             94                   8                                                                                  ##STR25##                            88        p-amino- benzoate                                                                     166                  9                                                                                  ##STR26##                            60   93                               10                                                                                 ##STR27##                            75   170  methane- sulfonate                                                                    185                  11                                                                                 ##STR28##                            78   amor- phous                      12                                                                                 ##STR29##                            74        hydrochloride                                                                         194                  13                                                                                 ##STR30##                            88        hydrochloride                                                                         215                  14                                                                                 ##STR31##                            84        maleate                                                                               209                  15                                                                                 ##STR32##                            66        succinate                                                                             168                  16                                                                                 ##STR33##                            66        sulfate                                                                               250                  17                                                                                 ##STR34##                            88   135                              18                                                                                 ##STR35##                            66   126                              19                                                                                 ##STR36##                            69.5 134                              20                                                                                 ##STR37##                            72        hydrochloride                                                                         252                  21                                                                                 ##STR38##                            87        sulfate                                                                               225                  22                                                                                 ##STR39##                            80        p-amino- benzoate                                                                     123                  23                                                                                 ##STR40##                            68        sulfate                     24                                                                                 ##STR41##                            82        hydrochloride                                                                         215                  25                                                                                 ##STR42##                            93   93                               26                                                                                 ##STR43##                            82        sulfate                                                                               183                  27                                                                                 ##STR44##                            80   68                               28                                                                                 ##STR45##                            61        maleate                                                                               137                  29                                                                                 ##STR46##                            81        maleate                                                                               123                  30                                                                                 ##STR47##                            70        hydrochloride                                                                         193                  31                                                                                 ##STR48##                            78        p-amino- benzoate                                                                     118                  32                                                                                 ##STR49##                            73   178  maleate                                                                               161                  33                                                                                 ##STR50##                            62        succinate                                                                             198                  34                                                                                 ##STR51##                            81   139  succinate                                                                             206                  35                                                                                 ##STR52##                            75   141  maleate                                                                               218                  36                                                                                 ##STR53##                            69        maleate                                                                               168                  37                                                                                 ##STR54##                            83        hydrochloride                                                                         196                  38                                                                                 ##STR55##                            67        succinate                                                                             180                  39                                                                                 ##STR56##                            84        maleate                                                                               170                  40                                                                                 ##STR57##                            69        hydrochloride                                                                         170                  41                                                                                 ##STR58##                            79        hydrochloride                                                                         116                  42                                                                                 ##STR59##                            70        maleate                                                                               210                  43                                                                                 ##STR60##                            68        hydrochloride                                                                         239                  44                                                                                 ##STR61##                            50        p-amino- benzoate                                                                     152,5                45                                                                                 ##STR62##                            53        p-amino- benzoate                                                                     159                  46                                                                                 ##STR63##                            38   163  hydrochloride                                                                         148                  47                                                                                 ##STR64##                            86        hydrochloride                                                                         183                  48                                                                                 ##STR65##                            88.5 116                              49                                                                                 ##STR66##                            95,4 122                              50                                                                                 ##STR67##                            84.5      hydrochloride                                                                         197                  51                                                                                 ##STR68##                            86        hydrochloride                                                                         142                  52                                                                                 ##STR69##                            83        hydrochloride                                                                         176                  53                                                                                 ##STR70##                            77   107                              54                                                                                 ##STR71##                            64        hydrochloride                                                                         233                  55                                                                                 ##STR72##                            75        maleate                                                                               218                  56                                                                                 ##STR73##                            70.3      hydrochloride                                                                         196                  57                                                                                 ##STR74##                            70.3 hydrochloride                                                                       181                         58                                                                                 ##STR75##                            62        sulfate                                                                               259                  59                                                                                 ##STR76##                            89   122  hydrochloride                                                                         172                  60                                                                                 ##STR77##                            87   108  maleate                                                                               242                  61                                                                                 ##STR78##                            83   127  hydrochloride                                                                         220                  62                                                                                 ##STR79##                            88   137  methane- sulfonate                                                                    170                  63                                                                                 ##STR80##                            79   183  hydrochloride                                                                         198                  64                                                                                 ##STR81##                            68   116  sulfate                                                                               248                  65                                                                                 ##STR82##                            86        Formate                                                                               143                  66                                                                                 ##STR83##                            78   112-114                                                                             hydrochloride .                                                                H.sub.2 O                                                                             227- 228             67                                                                                 ##STR84##                            71   84                               68                                                                                 ##STR85##                            73        hydrochloride                                                                         197                  69                                                                                 ##STR86##                            79   168  maleate                                                                               88                   70                                                                                 ##STR87##                            73        hydrochloride                                                                         187                  71                                                                                 ##STR88##                            69        hydrochloride                                                                         decomp.                                                                        >200°         72                                                                                 ##STR89##                                                                  73                                                                                 ##STR90##                                                                  74                                                                                 ##STR91##                                                                  75                                                                                 ##STR92##                                                                  76                                                                                 ##STR93##                                                                  77                                                                                 ##STR94##                                                                  78                                                                                 ##STR95##                                                                  79                                                                                 ##STR96##                                                                  80                                                                                 ##STR97##                                                                  81                                                                                 ##STR98##                                                                  82                                                                                 ##STR99##                                                                  83                                                                                 ##STR100##                                                                 __________________________________________________________________________

EXAMPLE 84

A mixture consisting of 42.5 gm of 3,4-dibenzyloxyphenyl-ω-bromoacetophenone, 29 gm of N-methyl-N'-(2-benzylamino-ethyl)-benzimidazolinone-(2), 25 gm of sodium carbonate and 600 ml of acetonitrile was refluxed for 2 hours. Thereafter, the precipitated inorganic products were filtered off, and the solvent was distilled out of the filtrate under a water aspirator vacuum in a rotary evaporator, the residue was taken up in 900 ml of methanol, 30 ml of an ethereal 12% hydrochloric acid solution and 15 ml of an ethereal 1% palladium chloride solution were added, and the mixture was hydrogenated in the presence of 2 gm of activated charcoal at 60° C. and 6 atmospheres until 3 molar equivalents of hydrogen had been absorbed. After separation of the catalyst, about half of the methanol was distilled off, and the residual solution was admixed with 500 ml of acetonitrile. 32 gm of 1-(3,4-dihydroxyphenyl)-1-oxo-2-[(3-methyl)-benzimidazolinone-(2)-yl]-ethylaninoethane hydrochloride crystallized out which, after recrystallization from water, had a melting point of 250° C. 8 gm of this aminoketone were hydrogenated in 400 ml of methanol in the presence of 1 gm of platinum oxide under standard conditions until 1 molar equivalent of hydrogen had been absorbed, and the hydrogenation product was isolated as its hydrochloride of the formula ##STR101## having a melting point of 185° C. The yield was 88% of theory.

Using an analogous procedure and corresponding starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE II                                     __________________________________________________________________________     Ex.                                     Yield %                                                                             m.p. of     m.p. of               No. Formula                             of theory                                                                           Base °C.                                                                     Salt   Salt                  __________________________________________________________________________                                                              °C.            85                                                                                  ##STR102##                         89        p-amino- benzoate                                                                     161                   86                                                                                  ##STR103##                         92        maleate                                                                               134                   87                                                                                  ##STR104##                         92        maleate                                                                               209                   88                                                                                  ##STR105##                         93        succinate                                                                             168                   89                                                                                  ##STR106##                         90        maleate                                                                               168                   90                                                                                  ##STR107##                         96        maleate                                                                               210                   91                                                                                  ##STR108##                         93        hydrochloride                                                                         239                   92                                                                                  ##STR109##                         94        p-amino- benzoate                                                                     159                   93                                                                                  ##STR110##                         88        hydrochloride                                                                         170                   94                                                                                  ##STR111##                         89        succinate                                                                             204                   95                                                                                  ##STR112##                         78        cyclamate                                                                             176                   96                                                                                  ##STR113##                         93   170  methane- sulfonate                                                                    185                   97                                                                                  ##STR114##                         90        maleate                                                                               138                   98                                                                                  ##STR115##                         94        maleate H.sub.2                                                                       180                   99                                                                                  ##STR116##                         85        maleate                                                                               157                   100                                                                                 ##STR117##                         92        maleate                                                                               180                   101                                                                                 ##STR118##                         90        hydrochloride . 2                                                              H.sub.2 O                                                                             275                   102                                                                                 ##STR119##                         94        hydrochloride                                                                         265                   103                                                                                 ##STR120##                         93        hydrochloride                                                                         177                   104                                                                                 ##STR121##                         89        succinate                                                                             215                   105                                                                                 ##STR122##                         92        succinate . H.sub.2                                                                   128                   106                                                                                 ##STR123##                         94        p-amino- benzoate                                                                     166                   107                                                                                 ##STR124##                         91        succinate                                                                             169-71                108                                                                                 ##STR125##                         90        p-amino benzoate                                                                      193                   109                                                                                 ##STR126##                         84        succinate                                                                             176                   110                                                                                 ##STR127##                         90   212  p-amino- benzoate                                                                     234                   111                                                                                 ##STR128##                         92   148  p-amino- benzoate                                                                     191                   112                                                                                 ##STR129##                         90        hydrochloride                                                                         190                   113                                                                                 ##STR130##                         89        succinate                                                                             189                   114                                                                                 ##STR131##                         90        Formiate . 1/2 CH.sub.3                                                        CN     159                   115                                                                                 ##STR132##                         93    95  hydrochloride                                                                         185                   116                                                                                 ##STR133##                         94        hydrochloride                                                                         198                   117                                                                                 ##STR134##                         93        p-amino- benzoate                                                                     199                   118                                                                                 ##STR135##                         90        hydrochloride                                                                         175                   119                                                                                 ##STR136##                         91   206  hydrochloride                                                                         169                   120                                                                                 ##STR137##                         94   200  hydrochloride                                                                         201                   121                                                                                 ##STR138##                         85   198  hydrochloride                                                                         157                   122                                                                                 ##STR139##                         92        succinate                                                                             198                   123                                                                                 ##STR140##                         89        acid maleate                                                                          202                   124                                                                                 ##STR141##                         97        acid maleate                                                                          180                   125                                                                                 ##STR142##                         92        acid maleate                                                                          168                   126                                                                                 ##STR143##                         89        hydrochloride                                                                         230                   127                                                                                 ##STR144##                         94        hydrochloride                                                                         252                   128                                                                                 ##STR145##                         90        succinate                                                                             173                   129                                                                                 ##STR146##                         91   198  hydrochloride                                                                         235                   130                                                                                 ##STR147##                         84        succinate                                                                             212                   131                                                                                 ##STR148##                         89        succinate                                                                             218                   132                                                                                 ##STR149##                         94   180  hydrochloride                                                                         190                   133                                                                                 ##STR150##                         88        formate                                                                               214                   134                                                                                 ##STR151##                         92   190  hydrochloride                                                                         225                   135                                                                                 ##STR152##                         87        hydrochloride                                                                         170                   136                                                                                 ##STR153##                         90   193  hydrochloride                                                                         196                   137                                                                                 ##STR154##                         96        maleate                                                                               210                   138                                                                                 ##STR155##                         96        hydrochloride                                                                         239                   139                                                                                 ##STR156##                         93        p-amino- benzoate                                                                     152.5                 140                                                                                 ##STR157##                         90        p-amino- benzoate                                                                     159                   141                                                                                 ##STR158##                         67   163  hydrochloride                                                                         148                   142                                                                                 ##STR159##                         81        p-amino- benzoate                                                                     190                   143                                                                                 ##STR160##                         79        hydrochloride                                                                         262                   144                                                                                 ##STR161##                         84        maleate                                                                               202                   145                                                                                 ##STR162##                         88        maleate                                                                               202                   146                                                                                 ##STR163##                         85   180  succinate                                                                             203                   147                                                                                 ##STR164##                         88        p-amino- benzoate                                                                     196                   148                                                                                 ##STR165##                         90   180  hydrochloride                                                                         193                   149                                                                                 ##STR166##                         72        hydrochloride                                                                         212                   150                                                                                 ##STR167##                         69        hydrochloride                                                                         182                   151                                                                                 ##STR168##                         76        hydrochloride                                                                         221                   152                                                                                 ##STR169##                         82   113  hydrochloride . H.sub.2                                                        O      80-82                 153                                                                                 ##STR170##                         79        formate                                                                               138                   154                                                                                 ##STR171##                         72        methanesul- fonate .                                                           H.sub.2 O                                                                             120                   155                                                                                 ##STR172##                         76        hydrochloride                                                                         252                   156                                                                                 ##STR173##                         81        sulfate                                                                               192                   157                                                                                 ##STR174##                         72        hydrochloride                                                                         209                   158                                                                                 ##STR175##                                   hydro- chloride .                                                              H.sub.2 O                                                                             173-176               159                                                                                 ##STR176##                         83        hydro- chloride                                                                       amorphous             160                                                                                 ##STR177##                         78   156  hydro- chloride                                                                       188                   161                                                                                 ##STR178##                         86        maleate                                                                               176                   162                                                                                 ##STR179##                         62        hydro- chloride                                                                       decomp. >230          163                                                                                 ##STR180##                         57        methane- sulfonate                                                                    decomp. >230          164                                                                                 ##STR181##                         67        hydro- chloride                                                                       decomp. >220          165                                                                                 ##STR182##                         58        sulfate                                                                               decomp. >240          166                                                                                 ##STR183##                         71        hydro- chloride                                                                       decomp. >230          167                                                                                 ##STR184##                         52        hydro- chloride                                                                       decomp. >230          168                                                                                 ##STR185##                         67        hydro- chloride                                                                       decomp. >220          169                                                                                 ##STR186##                         82        methane- sulfonate                                                                    decomp. >240          170                                                                                 ##STR187##                                   hydro- chloride                                                                       decomp. >230          171                                                                                 ##STR188##                         61        hydro- chloride                                                                       decomp. >240          172                                                                                 ##STR189##                         69        hydro- chloride                                                                       decomp. >220          __________________________________________________________________________

EXAMPLE 173

A solution of 9.1 gm of m-benzyloxy-ω-bromoacetophenone in 75 ml of ethanol was admixed at -5° C. with 1.2 gm of sodium borohydride, and the mixture was stirred for half an hour. The resulting solution was admixed with a little hydrobromic acid, the ethanol was distilled off under reduced pressure, and the residue was taken up in ethyl acetate. The solution was extracted first with an aqueous sodium bicarbonate solution and then with water, dried and evaporated in vacuo. The residue was taken up in 45 ml of dimethylformamide, admixed with 6.57 gm of 1-(4-amino-4,4-dimethylbutyl)-benzimidazolidinone-(2) and 6.65 gm of sodium carbonate, and the mixture was stirred for 6 hours at 105° C. After working up, the reaction product was isolated as its succinate of the formula ##STR190## which had a melting point of 94° C. The yield was 58% of theory.

Using an analogous procedure and corresponding starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE III                                    __________________________________________________________________________     Ex.                                    Yield %                                                                             m.p. of       m.p. of              No. Formula                            of theory                                                                           Base °C.                                                                     Salt     Salt                 __________________________________________________________________________                                                               °C.           174                                                                                 ##STR191##                        61        p-amino- benzoate                                                                       166                  175                                                                                 ##STR192##                        59    68                                176                                                                                 ##STR193##                        62        maleate  210                  177                                                                                 ##STR194##                        68        hydrochloride                                                                           239                  178                                                                                 ##STR195##                        76        p-amino benzoate                                                                        152.5                179                                                                                 ##STR196##                        73        p-amino- benzoate                                                                       159                  180                                                                                 ##STR197##                        64   122                                181                                                                                 ##STR198##                        64        sulfate  225                  182                                                                                 ##STR199##                        47   170  methane- sulfonate                                                                      185                  __________________________________________________________________________

EXAMPLE 183

By reacting 69.6 gm of the compound of the formula ##STR200## with 55.6 gm of chloroacetone in the presence of potassium carbonate and potassium iodide in acetone, followed by acid-catalyzed hydrolysis, 32 gm of the compound of the formula ##STR201## m.p. 182° C. were obtained. A solution of 19 gm of this substance in 300 ml of methanol was admixed with 25 ml of ammonia, and the mixture was hydrogenated with Raney nickel as the catalyst at 50° to 60° C. and 6 atmospheres. The hydrogenation product was isolated as its hydrochloride, m.p. 267°-270° C., of the formula ##STR202## The yield was 15.6 gm.

EXAMPLE 184

A mixture consisting of 35 gm of 3,4-dibenzyloxy-ω-bromoacetophenone, 24 gm of 1-(3-benzylamino-n-propyl)-benzimidazolinone-(2), 22 gm of sodium carbonate and 300 ml of acetonitrile was refluxed for 2 hours. The reaction product of the formula ##STR203## was isolated at its bioxalate with a yield of 44 gm (m.p. 168° C.). The free base (m.p. 112° C.) was liberated with aqueous ammonia. 35 gm of the base were dissolved in 350 ml of ethanol, 29 ml of 2 N sodium hydroxide were added to the solution, and then a total of 6 gm of sodium borohydride were added in portions over a period of 90 minutes. The reaction product of the formula ##STR204## was isolated as the free base (m.p. 93° C.).

A solution of 15 gm of the base in 150 ml of methanol was hydrogenated in the presence of 3 gm of palladized coal at 60° C. and 6 atmospheres until 3 molar equivalents of hydrogen had been absorbed. After removal of the catalyst, the solution was admixed with a solution of 2 gm of succinic acid in 20 ml of hot methanol, yielding 77% of theory of the crystalline succinate, m.p. 204° C., of the formula ##STR205##

Using analogous procedures and starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE IV                                     __________________________________________________________________________     Ex.                             Yield %                                                                             m.p. of     m.p. of                       No.                                                                                  Formula                   of theory                                                                           Base °C.                                                                     Salt   Salt °C.               __________________________________________________________________________     185                                                                                ##STR206##                  81   170  methane- sulfonate                                                                    185                           186                                                                                ##STR207##                  77        succinate                                                                             189                           187                                                                                ##STR208##                  62        hydrochloride                                                                         185                           188                                                                                ##STR209##                  91        hydrochloride                                                                         198                           189                                                                                ##STR210##                  82        hydrochloride                                                                         182                           __________________________________________________________________________

EXAMPLE 190

A solution of 7 gm of the compound of the formula ##STR211## in 200 ml of methanol was hydrogenated in the presence of 1 gm of palladized coal under standard conditions until 2 molar equivalents of hydrogen had been absorbed. The hydrogenation product was isolated with a yield of 94% of theory as its maleate (m.p. 180° C., with 1 mol of water of crystallization) of the formula ##STR212##

Using analogous procedures and starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE V                                      __________________________________________________________________________     Ex.                                    Yield %                                                                             m.p. of      m.p. of               No.                                                                               Formula                             of theory                                                                           Base °C.                                                                     Salt    Salt                  __________________________________________________________________________                                                              °C.            191                                                                                ##STR213##                         91        hydrochloride                                                                          185                   192                                                                                ##STR214##                         92        cyclamate                                                                              176                   193                                                                                ##STR215##                         89        maleate 134                   194                                                                                ##STR216##                         90        succinate                                                                              204                   195                                                                                ##STR217##                         90        hydrochloride                                                                          170                   196                                                                                ##STR218##                         85        hydrochloride                                                                          158                   197                                                                                ##STR219##                         86        maleate 168                   198                                                                                ##STR220##                         91        hydrochloride                                                                          265                   199                                                                                ##STR221##                         90        hydrochloride × 2                                                        H.sub.2 O                                                                              275                   200                                                                                ##STR222##                         85        maleate 180                   201                                                                                ##STR223##                         91        maleate 157                   202                                                                                ##STR224##                         94        maleate 138                   203                                                                                ##STR225##                         83        succinate                                                                              176                   204                                                                                ##STR226##                         93        p-amino- benzoate                                                                      193                   205                                                                                ##STR227##                         92        succinate                                                                              171                   206                                                                                ##STR228##                         93        succinate ×                                                              H.sub.2 O                                                                              128                   207                                                                                ##STR229##                         92        succinate                                                                              215                   208                                                                                ##STR230##                         90        hydrochloride                                                                          177                   209                                                                                ##STR231##                         84        formate 214                   210                                                                                ##STR232##                         90   190  hydrochloride                                                                          225                   211                                                                                ##STR233##                         82        hydrochloride                                                                          170                   212                                                                                ##STR234##                         93   193  hydrochloride                                                                          196                   213                                                                                ##STR235##                         9         hydrochloride                                                                          175                   214                                                                                ##STR236##                         94   206  hydrochloride                                                                          169                   215                                                                                ##STR237##                         91   200  hydrochloride                                                                          201                   216                                                                                ##STR238##                         86   198  hydrochloride                                                                          157                   217                                                                                ##STR239##                         84        acid maleate                                                                           202                   218                                                                                ##STR240##                         92        acid maleate                                                                           180                   219                                                                                ##STR241##                         92   212  p-amino- benzoate                                                                      234                   220                                                                                ##STR242##                         93   148  p-amino- benzoate                                                                      191                   221                                                                                ##STR243##                         92        hydrochloride                                                                          190                   222                                                                                ##STR244##                         86        succinate                                                                              189                   223                                                                                ##STR245##                         84        formate × 1/2                                                            CH.sub.3 CN                                                                            159                   224                                                                                ##STR246##                         89        hydrochloride                                                                          198                   225                                                                                ##STR247##                         90        p-amino- benzoate                                                                      199                   226                                                                                ##STR248##                         81        acid maleate                                                                           168                   227                                                                                ##STR249##                         81        hydrochloride                                                                          230                   228                                                                                ##STR250##                         84        hydrochloride                                                                          252                   229                                                                                ##STR251##                         90        succinate                                                                              173                   230                                                                                ##STR252##                         93   198  hydrochloride                                                                          235                   231                                                                                ##STR253##                         85        succinate                                                                              212                   232                                                                                ##STR254##                         82        succinate                                                                              218                   233                                                                                ##STR255##                         84   180  hydrochloride                                                                          190                   234                                                                                ##STR256##                         81        p-amino- benzoate                                                                      190                   235                                                                                ##STR257##                         82   180  succinate                                                                              203                   236                                                                                ##STR258##                         89        p-amino- benzoate                                                                      196                   237                                                                                ##STR259##                         92   180  hydrochloride                                                                          193                   238                                                                                ##STR260##                         82        hydrochloride                                                                          212                   239                                                                                ##STR261##                         79        hydrochloride                                                                          182                   240                                                                                ##STR262##                         79        hydrochloride                                                                          221                   241                                                                                ##STR263##                         80   113  hydrochloride ×                                                          H.sub.2 O                                                                              80-82                 242                                                                                ##STR264##                         75        formate 138                   243                                                                                ##STR265##                         82        methane- sulfonate                                                             × H.sub.2 O                                                                      120                   244                                                                                ##STR266##                         86        sulfate 192                   245                                                                                ##STR267##                         88   173  hydrochloride                                                                          203                   246                                                                                ##STR268##                         73.6 175  hydrochloride                                                                          216                   247                                                                                ##STR269##                         63        hydrochloride                                                                          181                   248                                                                                ##STR270##                         74   169  dihydro-  chloride                                                                     206                   249                                                                                ##STR271##                         72                                      250                                                                                ##STR272##                         69        hydro- chloride                                                                        amorphous             251                                                                                ##STR273##                         87   156  hydro- chloride                                                                        188                   252                                                                                ##STR274##                         75        maleate 176                   253                                                                                ##STR275##                         74        hydro-  chloride                                                                       decomp. >230          254                                                                                ##STR276##                         92        methane- sulfonate                                                                     decomp. >230          255                                                                                ##STR277##                         88        hydro- chloride                                                                        decomp. >220          256                                                                                ##STR278##                         87        sulfate decomp. >240          257                                                                                ##STR279##                         78        hydro- chloride                                                                        decomp. >230          258                                                                                ##STR280##                         80        hydro- chloride                                                                        decomp. >230          259                                                                                ##STR281##                         78        hydro- chloride                                                                        decomp. >220          260                                                                                ##STR282##                         72        methane- sulfonate                                                                     decomp. >240          261                                                                                ##STR283##                         81        hydro- chloride                                                                        decomp. >230          262                                                                                ##STR284##                         69                                      __________________________________________________________________________

EXAMPLE 263

A mixture consisting of 3.9 gm of the compound of the formula ##STR285## 2 gm of acetic acid anhydride and 40 ml of dimethylformamide was heated on a boiling water bath for 1 hour. Thereafter, the solvent was distilled off in vacuo, and the base was liberated with ammonia, taken up in ethyl acetate, and the solution was dried. The ethyl acetate was distilled off, and the base was admixed in acetonitrile with the calculated amount of maleic acid, yielding 3.5 gm of the maleate of the formula ##STR286## which had a melting point of 202° C. after recrystallization from methanol.

EXAMPLE 264

A solution of 6.1 gm of the compound of the formula ##STR287## in a mixture of 20 ml of water and 7.5 ml of glacial acetic acid was admixed with a solution of 1.41 gm of potassium cyanate in 7.5 ml of water at 35° C. After standing overnight, the base was liberated with ammonia, separated by extracting it three times with isobutanol and converted into the maleate of the formula ##STR288## were obtained. After recrystallization from water, it had a melting point of 202° C.

EXAMPLE 265

A mixture consisting of 5 gm of the compound of the formula ##STR289## 100 ml of methanol and 100 ml of a concentrated aqueous ammonia solution was gently heated until a solution had formed. The solution was allowed to stand for an extended period of time, during which 4.3 gm of the base (m.p. 198° C.) of the formula ##STR290## crystallized out. Its hydrochloride, obtained by acidifying an ethanolic solution of the base with hydrochloric acid, had a melting point of 235° C.

Using analogous procedures and corresponding starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE VI                                     __________________________________________________________________________     Ex.                                   Yield %                                                                             m.p. of       m.p. of               No.                                                                               Formula                            of theory                                                                           Base °C.                                                                      Salt    Salt                  __________________________________________________________________________                                                              °C.            266                                                                                ##STR291##                        83   172   hydrochloride                                                                          204                   267                                                                                ##STR292##                        86   113   hydrochloride ×                                                          H.sub.2 O                                                                              80-82                 268                                                                                ##STR293##                        84   180   hydrochloride                                                                          190                   269                                                                                ##STR294##                        84         hydrochloride                                                                          221                   270                                                                                ##STR295##                        91   190   hydrochloride                                                                          225                   271                                                                                ##STR296##                        86         hydrochloride                                                                          195                   272                                                                                ##STR297##                        83.5       hydrochloride                                                                          147                   273                                                                                ##STR298##                        77         hydrochloride                                                                          178 (decomp.)         274                                                                                ##STR299##                        95         hydrochloride                                                                          208 (decomp.)         275                                                                                ##STR300##                        90   145   hydrochloride                                                                          215 (decomp.)         276                                                                                ##STR301##                        88         hydrochloride                                                                          197 (decomp.)         277                                                                                ##STR302##                        63   157   hydro- chloride                                                                        137                   __________________________________________________________________________

EXAMPLE 278

69.6 gm of the compound of the formula ##STR303## and then a solution of 0.44 mol of 3-(dibenzylamino)-n-propyl chloride in 300 ml of absolute ethanol were added to a solution of 0.42 mol of sodium in 200 ml of absolute ethanol, and the mixture was refluxed for six hours. Thereafter, the precipitated sodium chloride was separated, and the liquid phase was admixed with 45 ml of concentrated sulfuric acid while stirring and cooling. After three hours 700 ml of water were added, the ethanol was distilled off, and the residual solution was made alkaline with ammonia, whereupon the compound of the formula ##STR304## precipitated out. Recrystallized from acetonitrile, the product had a melting point of 146° C.

60 gm of this compound were hydrogenated in a mixture of 400 ml of methanol and 200 ml of water in the presence of 16 ml of concentrated hydrochloric acid and palladized coal at 60° C. and 6 atmospheres until 1 molar equivalent of hydrogen had been absorbed. 88% of theory of the compound of the formula ##STR305## were obtained; it had a melting point of 60° C.

EXAMPLE 279

A solution of 53.4 gm of the compound of the formula ##STR306## in 420 ml of methanol and 80 ml of water was hydrogenated in the presence of 20 ml of concentrated hydrochloric acid and palladized coal at 60° C. and 6 atmospheres until 1 molar equivalent of hydrogen had been absorbed. 91% of theory of the hydrochloride (m.p. 315° C.) of the formula ##STR307## was obtained.

EXAMPLE 280

10.1 gm of sodium hydride and 45 gm of N-(3-chloro-n-propyl)-phthalimide were added to a solution of 31.1 gm of the compound of the formula ##STR308## in 150 ml of hexamethylphosphoric triamide (hexametapol) in an atmosphere of nitrogen, and the mixture was stirred for 5 hours at 100° C. The isolated raw reaction product of the formula ##STR309## was refluxed in 1 liter of ethanol with 13 gm of 85% hydrazine hydrate for 90 minutes, admixed with 21 ml of concentrated hydrochloric acid and 100 ml of water, and heated again for 20 minutes. The precipitated phthalic acid hydrazide was separated by suction filtration, and the hydrochloride (m.p. 195° C. from ethanol) of the formula ##STR310## was isolated.

EXAMPLE 281

3.3 gm of sodium hydride (55%) were added to a solution of 9.2 gm of the compound of the formula ##STR311## in 40 ml of absolute hexamethylphosphoric triamide in an atmosphere of nitrogen, and after the calculated amount of hydrogen had been released, a solution of 3-benzylamino-n-propyl chloride (b.p. 140° C. at 12 mm Hg) in 13 ml of hexamethylphosphoric triamide was added. The resulting mixture was stirred for 5 hours at 100° C., then poured over ice, and the reaction product of the formula ##STR312## was isolated by extraction with ether and hydrolyzed without purification with 2 N hydrochloric acid, yielding 67% of theory of the hydrochloride of the formula ##STR313## which had a melting point of 152°-155° C.

Using analogous procedures and corresponding starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE VII                                    __________________________________________________________________________     Ex.                               Yield %                                                                             m.p. of     m.p. of                     No.                                                                               Formula                        of theory                                                                           Base Salt   Salt                        __________________________________________________________________________                                                        °C.                  282                                                                                ##STR314##                    84.5 175  hydro- chloride ×                                                        H.sub.2 O                                                                             280                         283                                                                                ##STR315##                    54        hydrochlo- ride                                                                       150                         284                                                                                ##STR316##                    62        maleate                                                                               157                         285                                                                                ##STR317##                    55        hydro- chloride                                                                       214-216                     286                                                                                ##STR318##                    90        hydro- chloride                                                                       277-79                      __________________________________________________________________________     Ex.                               Yield %                                                                             m.p. of     m.p. of                     No.                                                                               Formula                        of theory                                                                           Base °C.                                                                     Salt   Salt                        __________________________________________________________________________                                                        °C.                  287                                                                                ##STR319##                    68        hydro- chloride                                                                       237-239                     288                                                                                ##STR320##                    75        hydro- chloride                                                                       266-268                     289                                                                                ##STR321##                    74   76   hydro- chloride ×                                                        H.sub.2 O                                                                             140.5                       290                                                                                ##STR322##                    92   135  hydro- chloride                                                                       306                         291                                                                                ##STR323##                    89        hydro- chloride                                                                       253                         292                                                                                ##STR324##                    65        p-amino- benzoate                                                                     245                         293                                                                                ##STR325##                    70        p-amino- benzoate                                                                     225                         294                                                                                ##STR326##                    82        p-amino- benzoate                                                                     233                         295                                                                                ##STR327##                    80        hydro- chloride                                                                       267-70                      296                                                                                ##STR328##                    62        maleate                                                                               179                         297                                                                                ##STR329##                    87   81                                      298                                                                                ##STR330##                    75        hydro- chloride                                                                       246                         299                                                                                ##STR331##                    72.3      hydrochloride                                                                         185                         300                                                                                ##STR332##                    61        hydrochloride                                                                         225                         301                                                                                ##STR333##                    60        hydrochloride                                                                         202                         302                                                                                ##STR334##                    89        hydrochloride                                                                         225                         __________________________________________________________________________

EXAMPLE 303

A solution of 174 gm of the compound of the formula ##STR335## in 700 ml of absolute hexamethylphosphoric triamide was admixed with 48 gm of sodium hydride in the form of a 55% suspension, and after the evolution of hydrogen had ceased, a solution of 341 gm of the compound of the formula ##STR336## (m.p. 76° C.) in 450 ml of hexamethylphosphoric triamide was added. The mixed solution was stirred for 5 hours at 100° C., then poured over ice, extracted with ether, and after evaporation of the ether from the extract the residue was dissolved in 3 liters of ethanol, and the solution was admixed with 300 ml of 5 N sulfuric acid. The next day the reaction product of the formula ##STR337## was isolated with a yield of 61% of theory (m.p. 198° C.). 58.75 gm of this compound were dissolved in 1700 ml of methanol, and after addition of Raney nickel the solution was hydrogenated at 6 atmospheres and 40°-60° C. The compound of the formula ##STR338## was isolated with a yield of 92% of theory (m.p. 135° C.). Its hydrochloride had a melting point of 306° C.

The compounds of the present invention, that is, those embraced by formula I above and their non-toxic, pharmacologically acceptable acid addition salts, have useful pharmacodynamic properties. More particularly, they exhibit coronary dilating and CNS-stimulating activities in warm-blooded animals, such as rats, guinea pigs and dogs, and are therefore useful as antihypertensives, bronchospasmolytics, circulation enhancers and antidepressants.

When R in formula I is a substituent group of the formula III, the nature of the variable substituents on the phenyl moiety thereof has an effect on the predominant pharmacological activity of these compounds.

For example, when R₅, R₆ and R₇ are lipophilic radicals or impart a lipophilic character to the substituent group of the formula III, the antidepressant activity predominates in these compounds. Such is the case, for instance, when R₅, R₆ and R₇ are hydrogen, halogen, alkoxy, amino, alkyl or trifluoromethyl, or when R₇ is hydrogen and R₅ and R₆ together with each other are ethylenedioxy or especially methylenedioxy.

When R₅, R₆ and R₇ are --OR₈ (where R₈ is hydrogen, acyl or aralkyl), --NH-acyl, amino or hydroxymethyl, or when R₅ and R₆ together with each other are --O--CH₂ --CONH--, --CH₂ -- CH₂ --CONH-- or --O--CONH-- and R₇ is hydroxyl, the vasodilating activity predominates in these compounds.

Finally, when R₅ is --OR₈ (where R₈ is hydrogen, acyl or aralkyl), R₆ is --CONHR₃ and R₇ is especially hydrogen, the antihypertensive activity predominates in these compounds.

Illustrative of the good pharmacological activity of the compounds of the present invention are the following data, where ##STR339##

Compound B, tested for peripheral vasodilation in dogs by measurement of the blood flow through the left hind extremity after intra-arterial administration, had a 22 times longer effective half-time and was 18 times more effective than the known vasodilator isoxsuprine.

Compound A, tested for antihypertensive activity on awake, genetically hypertonic rats, produced a decrease in blood pressure of 85 mm Hg at a dosage level of 30 mgm/kg i.p.

Compound C, tested for bronchospasmolytic activity in guinea pigs, was found to have a median effective dose ED₅₀ i.v. of 0.09 μgm/kg, whereas the corresponding ED₅₀ -value for the known, highly effective bronchospasmolytic isoproterenol is 3.0 μgm/kg.

For pharmaceutical purposes the compounds according to the present invention are administered to warm-blooded animals perorally, parenterally, rectally or by the inhalation route as active ingredients in customary dosage unit compositions, that is, compositions in dosage unit form consisting essentially of an inert pharmaceutical carrier and one effective dosage unit of the active ingredient, such as tablets, coated pills, capsules, wafers, powders, solutions, suspensions, emulsions, syrups, suppositories, inhalation sprays and the like. One effective dosage unit of the compounds according to the present invention is from 0.016 to 8.33 mgm/kg body weight, preferably 0.033 to 3.3 mgm/kg body weight, depending upon the form or mode of administration and the particular compound. The higher dosages are primarily adapted for sustained release compositions.

The following examples illustrate a few pharmaceutical dosage unit compositions comprising a compound of the present invention as an active ingredient and represent the best modes contemplated of putting the invention into practical use. The parts are parts by weight unless otherwise specified.

EXAMPLE 304

    ______________________________________                                         Tablets                                                                        The tablet composition is compounded from the                                  following ingredients:                                                         ______________________________________                                         1-(3,4-Methylenedioxy-phenyl)-2-[1,1-                                          dimethyl-3-(benzimidazolidin-2-one-                                            1-yl)-n-propyl-amino]-ethanol maleate                                          (see Example 55)         2 parts                                               Stearic acid             6 parts                                               Glucose                  592 parts                                             Total                    600 parts                                             ______________________________________                                    

Preparation

The ingredients are admixed in conventional manner, and the composition is compressed into 600 mgm-tablets. Each tablet contains 2 mgm of the active ingredient and is an oral dosage unit composition.

EXAMPLE 305 Suppositories

The suppository composition is compounded from the following ingredients:

    ______________________________________                                         1-(3,4-Methylenedioxy-phenyl)-2-[1,1-                                          dimethyl-3-(3-methylbenzimidazolidin-                                          2-one-1-yl)-n-propyl-amino]-ethanol                                            hydrochloride (see Example 63)                                                                          100 parts                                             Lactose, powdered        45 parts                                              Cocoa butter             1555 parts                                            Total                    1700 parts                                            ______________________________________                                    

Preparation

The ingredients are processed in conventional manner into 1700 mgm-suppositories, each of which contains 100 mgm of the active ingredient and is a rectal dosage unit composition.

EXAMPLE 306 Capsules

The capsule filler composition is compounded from the following ingredients:

    ______________________________________                                         1-(3-Carboxymethylamido-4-hydroxyphenyl)-                                      2-[1,1-dimethyl-3-(1,2,3,4-tetrahydro-                                         quinol-2-one-1-yl)-n-propyl-amino]-                                            ethanol hydrochloride (see Example 233)                                                                  200 parts                                            Lactose                   440 parts                                            Corn starch               360 parts                                            Total                     1000 parts                                           ______________________________________                                    

Preparation

The ingredients are intimately admixed, the mixture is milled into a powder, and 1000 mgm-portions of the powder are filled into gelatin capsules of suitable size. Each capsule is an oral dosage unit composition containing 200 mgm of the active ingredient.

Any one of the other compounds embraced by formula I or a non-toxic, pharmacologically acceptable acid addition salt thereof may be substituted for the particular active ingredient in Examples 304 through 306. Likewise, the amount of active ingredient in these illustrative examples may be varied to achieve the dosage unit range set forth above, and the amounts and nature of the inert pharmaceutical carrier ingredients may be varied to meet particular requirements.

While the present invention has been illustrated with the aid of certain specific embodiments thereof, it will be readily apparent to others skilled in the art that the invention is not limited to these particular embodiments, and that various changes and modifications may be made without departing from the spirit of the invention or the scope of the appended claims. 

We claim:
 1. A racemic or optically active compound of the formula

    Q--C.sub.n H.sub.2n --NH--R

wherein Q is ##STR340## where R₁ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, trifluoromethyl or amino;R₂ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or trifluoromethyl; and R₁ and R₂, together, are methylenedioxy or ethylenedioxy; n is an integer from 2 to 6, inclusive; and R is ##STR341## where R₄ is hydrogen, methyl or ethyl;R₅, R₆ and R₇, which may be identical to or different from each other, are each hydrogen, halogen, hydroxymethyl, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro, cyano, --CONHR₃, --CONHOH, --COOR₃, R₈ O--, methylsulfonylmethyl or, when one or two of R₅ through R₇ are other than halogen or trifluoromethyl, also --NR₃ R₉, whereR₃ is hydrogen or alkyl of 1 to 4 carbon atoms, R₈ is hydrogen, alkanoyl of 1 to 20 carbon atoms, or benzyl, and R₉ is hydrogen, lower alkanoyl, methanesulfonyl, carbamoyl, dimethylsulfamoyl, or alkoxycarbonyl of 2 to 5 carbon atoms, and R₅ and R₆, together are --O--CH₂ --O--, --O--CH₂ CH₂ --O--, --CH═CH--CH═CH--, --O--CH₂ --CONH--, --CH₂ --CH₂ --CONH-- or --O--CO--NH--,or a non-toxic, pharmacologically acceptable acid addition salt thereof.
 2. A compound of claim 1, which is 1-(3-methanesulfonamido-4-hydroxy-phenyl)-2-{1,1-dimethyl-3-[3-(3,4-dimethoxy-phenyl)-imidazolidin-2-one-1-yl]-n-propyl-amino}-ethanol or a non-toxic, pharmacologically acceptable acid addition salt thereof.
 3. A vasodilating or antidepressant pharmaceutical dosage unit composition consisting essentially of an inert pharmaceutical carrier and an effective vasodilating or anti-depressant amount of a compound of claim
 1. 4. The method of dilating the blood vessels or relieving depression in a warm-blooded animal in need thereof, which comprises perorally, parenterally or rectally administering to said animal an effective vasodilating or anti-depressant amount of a compound of claim
 1. 